HEADER HYDROLASE/HYDROLASE INHIBITOR 05-JAN-16 5HDV
TITLE BACE-1 INCOMPLEX WITH (7AR)-7A-(5-CYANOTHIOPHEN-2-YL)-6-(5-FLUORO-4-
TITLE 2 METHOXY-6-METHYLPYRIMIDIN-2-YL)-3-METHYL-4-OXOOCTAHYDRO-2H-PYRROLO[3,
TITLE 3 4-D]PYRIMIDIN-2-IMINIUM
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BETA-SECRETASE 1;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: UNP RESIDUES 41-454;
COMPND 5 SYNONYM: ASPARTYL PROTEASE 2,ASP 2,BETA-SITE AMYLOID PRECURSOR
COMPND 6 PROTEIN CLEAVING ENZYME 1,BETA-SITE APP CLEAVING ENZYME 1,MEMAPSIN-2,
COMPND 7 MEMBRANE-ASSOCIATED ASPARTIC PROTEASE 2;
COMPND 8 EC: 3.4.23.46;
COMPND 9 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 GENE: BACE1, BACE, KIAA1149;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS ALZHEIMER'S, ASPARTYL PROTEASE, HYDROLASE, HYDROLASE-HYDROLASE
KEYWDS 2 INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR P.ORTH
REVDAT 2 27-APR-16 5HDV 1 JRNL
REVDAT 1 16-MAR-16 5HDV 0
JRNL AUTH M.MANDAL,Y.WU,J.MISIASZEK,G.LI,A.BUEVICH,J.P.CALDWELL,X.LIU,
JRNL AUTH 2 R.D.MAZZOLA,P.ORTH,C.STRICKLAND,J.VOIGT,H.WANG,Z.ZHU,X.CHEN,
JRNL AUTH 3 M.GRZELAK,L.A.HYDE,R.KUVELKAR,P.T.LEACH,G.TERRACINA,L.ZHANG,
JRNL AUTH 4 Q.ZHANG,M.S.MICHENER,B.SMITH,K.COX,D.GROTZ,L.FAVREAU,
JRNL AUTH 5 K.MITRA,I.KAZAKEVICH,B.A.MCKITTRICK,W.GREENLEE,M.E.KENNEDY,
JRNL AUTH 6 E.M.PARKER,J.N.CUMMING,A.W.STAMFORD
JRNL TITL STRUCTURE-BASED DESIGN OF AN IMINOHETEROCYCLIC BETA-SITE
JRNL TITL 2 AMYLOID PRECURSOR PROTEIN CLEAVING ENZYME (BACE) INHIBITOR
JRNL TITL 3 THAT LOWERS CENTRAL A BETA IN NONHUMAN PRIMATES.
JRNL REF J.MED.CHEM. V. 59 3231 2016
JRNL REFN ISSN 0022-2623
JRNL PMID 26937601
JRNL DOI 10.1021/ACS.JMEDCHEM.5B01995
REMARK 2
REMARK 2 RESOLUTION. 1.71 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER 2.11.6
REMARK 3 AUTHORS : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,
REMARK 3 : PACIOREK,ROVERSI,SHARFF,SMART,VONRHEIN,
REMARK 3 : WOMACK,MATTHEWS,TEN EYCK,TRONRUD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.71
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 19.89
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 98.9
REMARK 3 NUMBER OF REFLECTIONS : 108867
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 CROSS-VALIDATION METHOD : THROUGHOUT
REMARK 3 FREE R VALUE TEST SET SELECTION : RANDOM
REMARK 3 R VALUE (WORKING + TEST SET) : 0.183
REMARK 3 R VALUE (WORKING SET) : 0.182
REMARK 3 FREE R VALUE : 0.204
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT : 5438
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : NULL
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 20
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 1.71
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 1.75
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 96.82
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 7792
REMARK 3 BIN R VALUE (WORKING + TEST SET) : 0.2226
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 7383
REMARK 3 BIN R VALUE (WORKING SET) : 0.2212
REMARK 3 BIN FREE R VALUE : 0.2469
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.25
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 409
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : NULL
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 6020
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 68
REMARK 3 SOLVENT ATOMS : 947
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 21.64
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 1.84220
REMARK 3 B22 (A**2) : -3.45340
REMARK 3 B33 (A**2) : 1.61120
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : 0.00000
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.206
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : NULL
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : NULL
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : NULL
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : NULL
REMARK 3
REMARK 3 REFERENCES: BLOW, D. (2002) ACTA CRYST D58, 792-797
REMARK 3 CRUICKSHANK, D.W.J. (1999) ACTA CRYST D55, 583-601
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.961
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.951
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 6256 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 8523 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 2082 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 142 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 956 ; 5.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 6256 ; 20.000 ; HARMONIC
REMARK 3 BAD NON-BONDED CONTACTS : NULL ; NULL ; NULL
REMARK 3 IMPROPER TORSIONS : NULL ; NULL ; NULL
REMARK 3 PSEUDOROTATION ANGLES : NULL ; NULL ; NULL
REMARK 3 CHIRAL IMPROPER TORSION : 796 ; 5.000 ; SEMIHARMONIC
REMARK 3 SUM OF OCCUPANCIES : NULL ; NULL ; NULL
REMARK 3 UTILITY DISTANCES : NULL ; NULL ; NULL
REMARK 3 UTILITY ANGLES : NULL ; NULL ; NULL
REMARK 3 UTILITY TORSION : NULL ; NULL ; NULL
REMARK 3 IDEAL-DIST CONTACT TERM : 8069 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.010
REMARK 3 BOND ANGLES (DEGREES) : 1.02
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 4.36
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 14.44
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 5HDV COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 12-JAN-16.
REMARK 100 THE DEPOSITION ID IS D_1000216883.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 01-MAR-07
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 7.0
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : APS
REMARK 200 BEAMLINE : 17-ID
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.0
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 210
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : DENZO
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 108994
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.710
REMARK 200 RESOLUTION RANGE LOW (A) : 20.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 98.9
REMARK 200 DATA REDUNDANCY : 4.000
REMARK 200 R MERGE (I) : 0.05900
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 11.6000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.71
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.74
REMARK 200 COMPLETENESS FOR SHELL (%) : 96.9
REMARK 200 DATA REDUNDANCY IN SHELL : 4.00
REMARK 200 R MERGE FOR SHELL (I) : 0.50300
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.900
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: NULL
REMARK 200 SOFTWARE USED: AMORE
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 58.34
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.95
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 15% PEG 3350, 200MM NA/K TARTRATE,
REMARK 280 100MM HEPES, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 277K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 21
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X+1/2,-Y,Z+1/2
REMARK 290 3555 -X,Y+1/2,-Z+1/2
REMARK 290 4555 X+1/2,-Y+1/2,-Z
REMARK 290
REMARK 290 WHERE NNN -> OPERATOR NUMBER
REMARK 290 MMM -> TRANSLATION VECTOR
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY TRANSFORMATIONS
REMARK 290 THE FOLLOWING TRANSFORMATIONS OPERATE ON THE ATOM/HETATM
REMARK 290 RECORDS IN THIS ENTRY TO PRODUCE CRYSTALLOGRAPHICALLY
REMARK 290 RELATED MOLECULES.
REMARK 290 SMTRY1 1 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 1 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 1 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 2 -1.000000 0.000000 0.000000 43.20500
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 65.64000
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 44.66000
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 65.64000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 43.20500
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 44.66000
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON
REMARK 300 BURIED SURFACE AREA.
REMARK 350
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS
REMARK 350 GIVEN BELOW. BOTH NON-CRYSTALLOGRAPHIC AND
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.
REMARK 350
REMARK 350 BIOMOLECULE: 1
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A
REMARK 350 BIOMT1 1 1.000000 0.000000 0.000000 0.00000
REMARK 350 BIOMT2 1 0.000000 1.000000 0.000000 0.00000
REMARK 350 BIOMT3 1 0.000000 0.000000 1.000000 0.00000
REMARK 350
REMARK 350 BIOMOLECULE: 2
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 APPLY THE FOLLOWING TO CHAINS: B
REMARK 350 BIOMT1 1 1.000000 0.000000 0.000000 0.00000
REMARK 350 BIOMT2 1 0.000000 1.000000 0.000000 0.00000
REMARK 350 BIOMT3 1 0.000000 0.000000 1.000000 0.00000
REMARK 465
REMARK 465 MISSING RESIDUES
REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)
REMARK 465
REMARK 465 M RES C SSSEQI
REMARK 465 LEU A 41
REMARK 465 ARG A 42
REMARK 465 LEU A 43
REMARK 465 PRO A 44
REMARK 465 ARG A 45
REMARK 465 GLU A 46
REMARK 465 THR A 47
REMARK 465 ASP A 48
REMARK 465 GLU A 49
REMARK 465 GLU A 50
REMARK 465 PRO A 51
REMARK 465 GLU A 52
REMARK 465 GLU A 53
REMARK 465 PRO A 54
REMARK 465 GLY A 55
REMARK 465 ARG A 56
REMARK 465 ARG A 57
REMARK 465 TYR A 132
REMARK 465 THR A 133
REMARK 465 GLN A 134
REMARK 465 VAL A 373
REMARK 465 ALA A 374
REMARK 465 THR A 375
REMARK 465 PRO A 448
REMARK 465 GLN A 449
REMARK 465 THR A 450
REMARK 465 ASP A 451
REMARK 465 GLU A 452
REMARK 465 SER A 453
REMARK 465 THR A 454
REMARK 465 LEU B 41
REMARK 465 ARG B 42
REMARK 465 LEU B 43
REMARK 465 PRO B 44
REMARK 465 ARG B 45
REMARK 465 GLU B 46
REMARK 465 THR B 47
REMARK 465 ASP B 48
REMARK 465 GLU B 49
REMARK 465 GLU B 50
REMARK 465 PRO B 51
REMARK 465 GLU B 52
REMARK 465 GLU B 53
REMARK 465 PRO B 54
REMARK 465 GLY B 55
REMARK 465 ARG B 56
REMARK 465 VAL B 373
REMARK 465 ALA B 374
REMARK 465 THR B 375
REMARK 465 ILE B 447
REMARK 465 PRO B 448
REMARK 465 GLN B 449
REMARK 465 THR B 450
REMARK 465 ASP B 451
REMARK 465 GLU B 452
REMARK 465 SER B 453
REMARK 465 THR B 454
REMARK 470
REMARK 470 MISSING ATOM
REMARK 470 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;
REMARK 470 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;
REMARK 470 I=INSERTION CODE):
REMARK 470 M RES CSSEQI ATOMS
REMARK 470 LYS A 136 CG CD CE NZ
REMARK 470 LYS A 168 CG CD CE NZ
REMARK 470 LYS A 203 CE NZ
REMARK 470 GLN A 224 CG CD OE1 NE2
REMARK 470 LYS A 275 CD CE NZ
REMARK 470 GLU A 441 CG CD OE1 OE2
REMARK 470 GLN B 134 CG CD OE1 NE2
REMARK 470 LYS B 203 CE NZ
REMARK 470 GLN B 224 CG CD OE1 NE2
REMARK 470 LYS B 300 CE NZ
REMARK 470 GLU B 441 CG CD OE1 OE2
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: TORSION ANGLES
REMARK 500
REMARK 500 TORSION ANGLES OUTSIDE THE EXPECTED RAMACHANDRAN REGIONS:
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT:(10X,I3,1X,A3,1X,A1,I4,A1,4X,F7.2,3X,F7.2)
REMARK 500
REMARK 500 EXPECTED VALUES: GJ KLEYWEGT AND TA JONES (1996). PHI/PSI-
REMARK 500 CHOLOGY: RAMACHANDRAN REVISITED. STRUCTURE 4, 1395 - 1400
REMARK 500
REMARK 500 M RES CSSEQI PSI PHI
REMARK 500 HIS A 150 62.87 -107.05
REMARK 500 TRP A 258 -83.74 -144.34
REMARK 500 ALA A 333 121.51 -38.90
REMARK 500 HIS B 150 55.64 -107.54
REMARK 500 TRP B 258 -84.00 -143.90
REMARK 500 ALA B 333 122.00 -38.37
REMARK 500
REMARK 500 REMARK: NULL
REMARK 525
REMARK 525 SOLVENT
REMARK 525
REMARK 525 THE SOLVENT MOLECULES HAVE CHAIN IDENTIFIERS THAT
REMARK 525 INDICATE THE POLYMER CHAIN WITH WHICH THEY ARE MOST
REMARK 525 CLOSELY ASSOCIATED. THE REMARK LISTS ALL THE SOLVENT
REMARK 525 MOLECULES WHICH ARE MORE THAN 5A AWAY FROM THE
REMARK 525 NEAREST POLYMER CHAIN (M = MODEL NUMBER;
REMARK 525 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE
REMARK 525 NUMBER; I=INSERTION CODE):
REMARK 525
REMARK 525 M RES CSSEQI
REMARK 525 HOH A1061 DISTANCE = 6.17 ANGSTROMS
REMARK 525 HOH B1086 DISTANCE = 6.02 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 60V A 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue TLA B 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 60V B 502
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 5HE5 RELATED DB: PDB
REMARK 900 RELATED ID: 5HE4 RELATED DB: PDB
REMARK 900 RELATED ID: 5HDZ RELATED DB: PDB
REMARK 900 RELATED ID: 5HDX RELATED DB: PDB
REMARK 900 RELATED ID: 5HDU RELATED DB: PDB
REMARK 900 RELATED ID: 5HE7 RELATED DB: PDB
REMARK 900 RELATED ID: 5HD0 RELATED DB: PDB
DBREF 5HDV A 41 454 UNP P56817 BACE1_HUMAN 41 454
DBREF 5HDV B 41 454 UNP P56817 BACE1_HUMAN 41 454
SEQRES 1 A 414 LEU ARG LEU PRO ARG GLU THR ASP GLU GLU PRO GLU GLU
SEQRES 2 A 414 PRO GLY ARG ARG GLY SER PHE VAL GLU MET VAL ASP ASN
SEQRES 3 A 414 LEU ARG GLY LYS SER GLY GLN GLY TYR TYR VAL GLU MET
SEQRES 4 A 414 THR VAL GLY SER PRO PRO GLN THR LEU ASN ILE LEU VAL
SEQRES 5 A 414 ASP THR GLY SER SER ASN PHE ALA VAL GLY ALA ALA PRO
SEQRES 6 A 414 HIS PRO PHE LEU HIS ARG TYR TYR GLN ARG GLN LEU SER
SEQRES 7 A 414 SER THR TYR ARG ASP LEU ARG LYS GLY VAL TYR VAL PRO
SEQRES 8 A 414 TYR THR GLN GLY LYS TRP GLU GLY GLU LEU GLY THR ASP
SEQRES 9 A 414 LEU VAL SER ILE PRO HIS GLY PRO ASN VAL THR VAL ARG
SEQRES 10 A 414 ALA ASN ILE ALA ALA ILE THR GLU SER ASP LYS PHE PHE
SEQRES 11 A 414 ILE ASN GLY SER ASN TRP GLU GLY ILE LEU GLY LEU ALA
SEQRES 12 A 414 TYR ALA GLU ILE ALA ARG PRO ASP ASP SER LEU GLU PRO
SEQRES 13 A 414 PHE PHE ASP SER LEU VAL LYS GLN THR HIS VAL PRO ASN
SEQRES 14 A 414 LEU PHE SER LEU GLN LEU CYS GLY ALA GLY PHE PRO LEU
SEQRES 15 A 414 ASN GLN SER GLU VAL LEU ALA SER VAL GLY GLY SER MET
SEQRES 16 A 414 ILE ILE GLY GLY ILE ASP HIS SER LEU TYR THR GLY SER
SEQRES 17 A 414 LEU TRP TYR THR PRO ILE ARG ARG GLU TRP TYR TYR GLU
SEQRES 18 A 414 VAL ILE ILE VAL ARG VAL GLU ILE ASN GLY GLN ASP LEU
SEQRES 19 A 414 LYS MET ASP CYS LYS GLU TYR ASN TYR ASP LYS SER ILE
SEQRES 20 A 414 VAL ASP SER GLY THR THR ASN LEU ARG LEU PRO LYS LYS
SEQRES 21 A 414 VAL PHE GLU ALA ALA VAL LYS SER ILE LYS ALA ALA SER
SEQRES 22 A 414 SER THR GLU LYS PHE PRO ASP GLY PHE TRP LEU GLY GLU
SEQRES 23 A 414 GLN LEU VAL CYS TRP GLN ALA GLY THR THR PRO TRP ASN
SEQRES 24 A 414 ILE PHE PRO VAL ILE SER LEU TYR LEU MET GLY GLU VAL
SEQRES 25 A 414 THR ASN GLN SER PHE ARG ILE THR ILE LEU PRO GLN GLN
SEQRES 26 A 414 TYR LEU ARG PRO VAL GLU ASP VAL ALA THR SER GLN ASP
SEQRES 27 A 414 ASP CYS TYR LYS PHE ALA ILE SER GLN SER SER THR GLY
SEQRES 28 A 414 THR VAL MET GLY ALA VAL ILE MET GLU GLY PHE TYR VAL
SEQRES 29 A 414 VAL PHE ASP ARG ALA ARG LYS ARG ILE GLY PHE ALA VAL
SEQRES 30 A 414 SER ALA CYS HIS VAL HIS ASP GLU PHE ARG THR ALA ALA
SEQRES 31 A 414 VAL GLU GLY PRO PHE VAL THR LEU ASP MET GLU ASP CYS
SEQRES 32 A 414 GLY TYR ASN ILE PRO GLN THR ASP GLU SER THR
SEQRES 1 B 414 LEU ARG LEU PRO ARG GLU THR ASP GLU GLU PRO GLU GLU
SEQRES 2 B 414 PRO GLY ARG ARG GLY SER PHE VAL GLU MET VAL ASP ASN
SEQRES 3 B 414 LEU ARG GLY LYS SER GLY GLN GLY TYR TYR VAL GLU MET
SEQRES 4 B 414 THR VAL GLY SER PRO PRO GLN THR LEU ASN ILE LEU VAL
SEQRES 5 B 414 ASP THR GLY SER SER ASN PHE ALA VAL GLY ALA ALA PRO
SEQRES 6 B 414 HIS PRO PHE LEU HIS ARG TYR TYR GLN ARG GLN LEU SER
SEQRES 7 B 414 SER THR TYR ARG ASP LEU ARG LYS GLY VAL TYR VAL PRO
SEQRES 8 B 414 TYR THR GLN GLY LYS TRP GLU GLY GLU LEU GLY THR ASP
SEQRES 9 B 414 LEU VAL SER ILE PRO HIS GLY PRO ASN VAL THR VAL ARG
SEQRES 10 B 414 ALA ASN ILE ALA ALA ILE THR GLU SER ASP LYS PHE PHE
SEQRES 11 B 414 ILE ASN GLY SER ASN TRP GLU GLY ILE LEU GLY LEU ALA
SEQRES 12 B 414 TYR ALA GLU ILE ALA ARG PRO ASP ASP SER LEU GLU PRO
SEQRES 13 B 414 PHE PHE ASP SER LEU VAL LYS GLN THR HIS VAL PRO ASN
SEQRES 14 B 414 LEU PHE SER LEU GLN LEU CYS GLY ALA GLY PHE PRO LEU
SEQRES 15 B 414 ASN GLN SER GLU VAL LEU ALA SER VAL GLY GLY SER MET
SEQRES 16 B 414 ILE ILE GLY GLY ILE ASP HIS SER LEU TYR THR GLY SER
SEQRES 17 B 414 LEU TRP TYR THR PRO ILE ARG ARG GLU TRP TYR TYR GLU
SEQRES 18 B 414 VAL ILE ILE VAL ARG VAL GLU ILE ASN GLY GLN ASP LEU
SEQRES 19 B 414 LYS MET ASP CYS LYS GLU TYR ASN TYR ASP LYS SER ILE
SEQRES 20 B 414 VAL ASP SER GLY THR THR ASN LEU ARG LEU PRO LYS LYS
SEQRES 21 B 414 VAL PHE GLU ALA ALA VAL LYS SER ILE LYS ALA ALA SER
SEQRES 22 B 414 SER THR GLU LYS PHE PRO ASP GLY PHE TRP LEU GLY GLU
SEQRES 23 B 414 GLN LEU VAL CYS TRP GLN ALA GLY THR THR PRO TRP ASN
SEQRES 24 B 414 ILE PHE PRO VAL ILE SER LEU TYR LEU MET GLY GLU VAL
SEQRES 25 B 414 THR ASN GLN SER PHE ARG ILE THR ILE LEU PRO GLN GLN
SEQRES 26 B 414 TYR LEU ARG PRO VAL GLU ASP VAL ALA THR SER GLN ASP
SEQRES 27 B 414 ASP CYS TYR LYS PHE ALA ILE SER GLN SER SER THR GLY
SEQRES 28 B 414 THR VAL MET GLY ALA VAL ILE MET GLU GLY PHE TYR VAL
SEQRES 29 B 414 VAL PHE ASP ARG ALA ARG LYS ARG ILE GLY PHE ALA VAL
SEQRES 30 B 414 SER ALA CYS HIS VAL HIS ASP GLU PHE ARG THR ALA ALA
SEQRES 31 B 414 VAL GLU GLY PRO PHE VAL THR LEU ASP MET GLU ASP CYS
SEQRES 32 B 414 GLY TYR ASN ILE PRO GLN THR ASP GLU SER THR
HET 60V A 501 29
HET TLA B 501 10
HET 60V B 502 29
HETNAM 60V 5-[(2E,4AR,7AR)-6-(5-FLUORO-4-METHOXY-6-
HETNAM 2 60V METHYLPYRIMIDIN-2-YL)-2-IMINO-3-METHYL-4-OXOOCTAHYDRO-
HETNAM 3 60V 7AH-PYRROLO[3,4-D]PYRIMIDIN-7A-YL]THIOPHENE-2-
HETNAM 4 60V CARBONITRILE
HETNAM TLA L(+)-TARTARIC ACID
FORMUL 3 60V 2(C18 H18 F N7 O2 S)
FORMUL 4 TLA C4 H6 O6
FORMUL 6 HOH *947(H2 O)
HELIX 1 AA1 GLN A 114 SER A 118 5 5
HELIX 2 AA2 TYR A 184 ALA A 188 5 5
HELIX 3 AA3 PRO A 196 THR A 205 1 10
HELIX 4 AA4 ASN A 223 SER A 230 1 8
HELIX 5 AA5 ASP A 241 SER A 243 5 3
HELIX 6 AA6 ASP A 277 TYR A 283 5 7
HELIX 7 AA7 LYS A 299 SER A 313 1 15
HELIX 8 AA8 PRO A 319 LEU A 324 1 6
HELIX 9 AA9 PRO A 337 PHE A 341 5 5
HELIX 10 AB1 LEU A 362 TYR A 366 1 5
HELIX 11 AB2 GLY A 395 GLU A 400 1 6
HELIX 12 AB3 ASP A 439 GLY A 444 5 6
HELIX 13 AB4 GLN B 114 SER B 118 5 5
HELIX 14 AB5 TYR B 184 ALA B 188 5 5
HELIX 15 AB6 PRO B 196 THR B 205 1 10
HELIX 16 AB7 ASN B 223 SER B 230 1 8
HELIX 17 AB8 ASP B 241 SER B 243 5 3
HELIX 18 AB9 ASP B 277 TYR B 283 5 7
HELIX 19 AC1 LYS B 299 SER B 313 1 15
HELIX 20 AC2 PRO B 319 LEU B 324 1 6
HELIX 21 AC3 PRO B 337 PHE B 341 5 5
HELIX 22 AC4 LEU B 362 TYR B 366 1 5
HELIX 23 AC5 GLY B 395 GLU B 400 1 6
HELIX 24 AC6 ASP B 439 GLY B 444 5 6
SHEET 1 AA1 8 LEU A 67 LYS A 70 0
SHEET 2 AA1 8 GLY A 74 VAL A 81 -1 O TYR A 76 N ARG A 68
SHEET 3 AA1 8 GLN A 86 ASP A 93 -1 O VAL A 92 N TYR A 75
SHEET 4 AA1 8 GLY A 178 GLY A 181 1 O LEU A 180 N LEU A 91
SHEET 5 AA1 8 PHE A 99 GLY A 102 -1 N ALA A 100 O ILE A 179
SHEET 6 AA1 8 VAL A 156 ASP A 167 1 O ILE A 163 N VAL A 101
SHEET 7 AA1 8 LYS A 136 SER A 147 -1 N GLU A 140 O ALA A 162
SHEET 8 AA1 8 ARG A 122 VAL A 130 -1 N LYS A 126 O LEU A 141
SHEET 1 AA2 4 LEU A 67 LYS A 70 0
SHEET 2 AA2 4 GLY A 74 VAL A 81 -1 O TYR A 76 N ARG A 68
SHEET 3 AA2 4 LYS A 136 SER A 147 -1 O SER A 147 N THR A 80
SHEET 4 AA2 4 ARG A 122 VAL A 130 -1 N LYS A 126 O LEU A 141
SHEET 1 AA3 5 GLY A 233 ILE A 237 0
SHEET 2 AA3 5 PHE A 211 LEU A 215 -1 N GLN A 214 O SER A 234
SHEET 3 AA3 5 PHE A 402 ASP A 407 -1 O VAL A 404 N LEU A 213
SHEET 4 AA3 5 ARG A 412 SER A 418 -1 O ALA A 416 N TYR A 403
SHEET 5 AA3 5 TYR A 245 PRO A 253 -1 N THR A 252 O ILE A 413
SHEET 1 AA4 5 GLU A 261 VAL A 262 0
SHEET 2 AA4 5 SER A 286 VAL A 288 -1 O SER A 286 N VAL A 262
SHEET 3 AA4 5 THR A 392 MET A 394 1 O MET A 394 N ILE A 287
SHEET 4 AA4 5 LEU A 295 PRO A 298 -1 N ARG A 296 O VAL A 393
SHEET 5 AA4 5 ILE A 385 SER A 388 1 O SER A 386 N LEU A 297
SHEET 1 AA5 5 GLN A 272 ASP A 273 0
SHEET 2 AA5 5 ILE A 264 ILE A 269 -1 N ILE A 269 O GLN A 272
SHEET 3 AA5 5 ILE A 344 MET A 349 -1 O TYR A 347 N ARG A 266
SHEET 4 AA5 5 GLN A 355 ILE A 361 -1 O ILE A 361 N ILE A 344
SHEET 5 AA5 5 ALA A 430 VAL A 436 -1 O GLU A 432 N ARG A 358
SHEET 1 AA6 3 VAL A 329 TRP A 331 0
SHEET 2 AA6 3 ASP A 379 PHE A 383 -1 O ASP A 379 N TRP A 331
SHEET 3 AA6 3 LEU A 367 VAL A 370 -1 N ARG A 368 O LYS A 382
SHEET 1 AA7 8 LEU B 67 LYS B 70 0
SHEET 2 AA7 8 GLY B 74 VAL B 81 -1 O TYR B 76 N ARG B 68
SHEET 3 AA7 8 GLN B 86 ASP B 93 -1 O VAL B 92 N TYR B 75
SHEET 4 AA7 8 GLY B 178 GLY B 181 1 O LEU B 180 N LEU B 91
SHEET 5 AA7 8 PHE B 99 GLY B 102 -1 N ALA B 100 O ILE B 179
SHEET 6 AA7 8 VAL B 156 ASP B 167 1 O ILE B 163 N VAL B 101
SHEET 7 AA7 8 LYS B 136 SER B 147 -1 N GLU B 140 O ALA B 162
SHEET 8 AA7 8 ARG B 122 PRO B 131 -1 N VAL B 130 O TRP B 137
SHEET 1 AA8 4 LEU B 67 LYS B 70 0
SHEET 2 AA8 4 GLY B 74 VAL B 81 -1 O TYR B 76 N ARG B 68
SHEET 3 AA8 4 LYS B 136 SER B 147 -1 O SER B 147 N THR B 80
SHEET 4 AA8 4 ARG B 122 PRO B 131 -1 N VAL B 130 O TRP B 137
SHEET 1 AA9 5 GLY B 233 ILE B 237 0
SHEET 2 AA9 5 PHE B 211 LEU B 215 -1 N GLN B 214 O SER B 234
SHEET 3 AA9 5 PHE B 402 ASP B 407 -1 O VAL B 404 N LEU B 213
SHEET 4 AA9 5 ARG B 412 SER B 418 -1 O ALA B 416 N TYR B 403
SHEET 5 AA9 5 TYR B 245 PRO B 253 -1 N THR B 252 O ILE B 413
SHEET 1 AB1 5 GLU B 261 VAL B 262 0
SHEET 2 AB1 5 SER B 286 VAL B 288 -1 O SER B 286 N VAL B 262
SHEET 3 AB1 5 THR B 392 MET B 394 1 O MET B 394 N ILE B 287
SHEET 4 AB1 5 LEU B 295 PRO B 298 -1 N ARG B 296 O VAL B 393
SHEET 5 AB1 5 ILE B 385 SER B 388 1 O SER B 386 N LEU B 297
SHEET 1 AB2 5 GLN B 272 ASP B 273 0
SHEET 2 AB2 5 ILE B 264 ILE B 269 -1 N ILE B 269 O GLN B 272
SHEET 3 AB2 5 ILE B 344 MET B 349 -1 O TYR B 347 N ARG B 266
SHEET 4 AB2 5 GLN B 355 ILE B 361 -1 O ILE B 361 N ILE B 344
SHEET 5 AB2 5 ALA B 430 VAL B 436 -1 O GLU B 432 N ARG B 358
SHEET 1 AB3 3 VAL B 329 TRP B 331 0
SHEET 2 AB3 3 ASP B 379 PHE B 383 -1 O ASP B 379 N TRP B 331
SHEET 3 AB3 3 LEU B 367 VAL B 370 -1 N ARG B 368 O LYS B 382
SSBOND 1 CYS A 216 CYS A 420 1555 1555 2.06
SSBOND 2 CYS A 278 CYS A 443 1555 1555 2.05
SSBOND 3 CYS A 330 CYS A 380 1555 1555 2.07
SSBOND 4 CYS B 216 CYS B 420 1555 1555 2.07
SSBOND 5 CYS B 278 CYS B 443 1555 1555 2.04
SSBOND 6 CYS B 330 CYS B 380 1555 1555 2.05
CISPEP 1 SER A 83 PRO A 84 0 -1.82
CISPEP 2 ARG A 189 PRO A 190 0 2.30
CISPEP 3 TYR A 283 ASP A 284 0 1.27
CISPEP 4 GLY A 433 PRO A 434 0 -2.72
CISPEP 5 SER B 83 PRO B 84 0 -0.90
CISPEP 6 ARG B 189 PRO B 190 0 1.46
CISPEP 7 TYR B 283 ASP B 284 0 1.63
CISPEP 8 GLY B 433 PRO B 434 0 -4.22
SITE 1 AC1 13 GLN A 73 LEU A 91 ASP A 93 SER A 96
SITE 2 AC1 13 ASN A 98 TRP A 137 ARG A 189 ASP A 289
SITE 3 AC1 13 GLY A 291 THR A 292 HOH A 766 HOH A 816
SITE 4 AC1 13 HOH A 883
SITE 1 AC2 9 ARG B 68 ASN B 89 HIS B 110 ARG B 111
SITE 2 AC2 9 ASN B 175 HOH B 601 HOH B 715 HOH B 771
SITE 3 AC2 9 HOH B 877
SITE 1 AC3 17 GLN B 73 LEU B 91 ASP B 93 SER B 96
SITE 2 AC3 17 ASN B 98 VAL B 130 TYR B 132 TRP B 137
SITE 3 AC3 17 ILE B 171 ILE B 179 ASP B 289 GLY B 291
SITE 4 AC3 17 THR B 292 HOH B 804 HOH B 833 HOH B 834
SITE 5 AC3 17 HOH B 889
CRYST1 86.410 89.320 131.280 90.00 90.00 90.00 P 21 21 21 8
ORIGX1 1.000000 0.000000 0.000000 0.00000
ORIGX2 0.000000 1.000000 0.000000 0.00000
ORIGX3 0.000000 0.000000 1.000000 0.00000
SCALE1 0.011573 0.000000 0.000000 0.00000
SCALE2 0.000000 0.011196 0.000000 0.00000
SCALE3 0.000000 0.000000 0.007617 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
